Amino group (—NH2) or hydroxyl group (—OH) is one of the most important functional groups and contained in many useful compounds including pharmaceutical products and intermediates for synthesizing such products.
An amino group reacts very easily with a variety of reagents and it is therefore necessary to have the high reactivity of the amino group masked by a protecting group, followed by deprotection or deblocking at the final stage of synthesis so as to restore the original amino group. A versatile protecting group for an amino group is carbamate-based protecting group such as Boc group or Fmoc group, both of which have become indispensable protecting groups for peptide synthesis.
Acyl group, typified by acetyl group, is widely used as a protecting group for hydroxyl group, but its use as a protecting group for amino group is very limited. This is because an amide bond is thermodynamically very stable as compared with an ester bond, and therefore the deprotection for an acyl group needs to be carried out under strong acidic conditions (e.g. using hydrochloric acid or sulfuric acid) or basic conditions (e.g. using sodium hydroxide) so as to promote a hydrolysis reaction, generally at a high temperature exceeding 100° C. Thus, there is a restriction that the reaction can be applied only to stable substrates having no functionalized groups and hence being able to resist under such severe conditions.
On the other hand, an acyl group is a preferable protecting group in terms of chemical process, as compared with the abovementioned carbamate group, because it can coexist with various types of reactants and can be introduced inexpensively. The products of asymmetric hydrogenation reaction (which products are widely used in the synthesis of optically active α-amino acids) are almost completely limited to N-acyl amino acid derivatives. Consequently, N-deacylation reaction under a mild condition would make it possible to greatly improve the efficiency of the current synthesis process for medical products. However, there have been hitherto developed no methods other than the enzymic method, by which amide bonds can be hydrolyzed for deacylation under a mild condition.
As compounds having CO-containing atomic groups like amides, there are known cyclic carbamates, chain carbamates, cyclic carbonates, chain carbonates, cyclic ureas, chain ureas and the like, all of which contain a carbonyl group. These compounds are also important for obtaining useful compounds having an amino group and/or a hydroxyl group and other purposes. For example, cyclic carbamates are utilized in the synthesis and protection of amino alcohol and have recently attracted attention as synthetic intermediates obtained by activation of the C—H bond [e.g. Angew. Chem., Int. Ed. 2001, 40, 598 (Non-patent reference No. 1): Org. Lett. 2012, 14, 1386 (Non-patent reference No. 2)]. However, the decarbonylation of a cyclic carbamate generally requires a strong basic condition using barium hydroxide or lithium hydroxide and therefore has room for improvement in substrate versatility.